Bacterial infections are commonly associated with many diseases and disorders. Some bacteria form highly organized and uniquely structured communities known as biofilms and it is believed that the structure of biofilms and the altered physiology of biofilm bacteria allows bacteria to resist conventional front-line antibiotics and/or human phagocytes. One such biofilm-forming bacterium is Pseudomonas aeruginosa. Pseudomonas aeruginosa (PA or P. aeruginosa) is a gram-negative bacterium that rarely causes disease in healthy subjects, but is a dominant, opportunistic pathogen adversely affecting patients in diseases such as cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). PA is also one of the most common pathogens observed in intensive care units (ICUs) (Jarvis, W. R. et al., 1992, J. Antimicrob. Chemother. 29 (a supp.):19-24). Mortality rates as high as 50% have been reported from PA infections.
Interestingly, there is solid evidence in the literature that at least in CF subjects, some populations of PA are growing either microaerobically (Alvarez-Ortega C, and Harwood C S. 2007 Mol Microbiol 65:153-165.) or anaerobically, in the deepest mucus pockets (Worlitzsch D, et al. 2002. J. Clin. Invest. 109:317-325; Yoon S S, et al. 2002. Dev Cell 3:593-603; Hassett D J, et al. 2002. Adv Drug Deliv Rev 54:1425-1443; Hassett D J, et al. 2004, In, Strict and Facultative Anaerobes: Medical and Environmental Aspects: 87-108).
What is therefore needed are new therapeutic approaches for treating bacterial infections. Of particular importance are Burkholderia cepacia and S. aureus infections, and more particularly, P. aeruginosa infections in patients with CF or COPD, but new therapeutic approaches are needed for other gram negative bacterial infections as well